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Ann Oncol. 2015 Dec;26(12):2408-19. doi: 10.1093/annonc/mdv374. Epub 2015 Sep 7.

Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies.

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Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino-IST, Genova.
Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova.
Fertility and Procreation Unit, Gynecologic Oncology Department, European Institute of Oncology, Milan, Italy.
BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Department of Internal Medicine, University of Genoa, Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova, Italy.
German Breast Group (GBG), Neu-Isenburg Sana-Klinikum Offenbach, Offenbach am Main, Germany.
Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino-IST, Genova, Italy



The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS).


A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models.


A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I(2) = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I(2) = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I(2) = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I(2) = 68.0%, Pheterogeneity = 0.044).


Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.


breast cancer; fertility preservation; luteinizing hormone-releasing hormone agonists; ovarian function preservation; premenopausal patients

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